Rituximab With or Without Lenalidomide in Treating Patients With Previously Untreated Follicular Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier:
NCT01307605
First received: March 1, 2011
Last updated: December 8, 2013
Last verified: December 2013
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer cell growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Lenalidomide may stop the growth of non-Hodgkin lymphoma by blocking blood flow to the cancer. It is not yet known whether rituximab is more effective when given alone or together with lenalidomide in treating patients with follicular lymphoma.

PURPOSE: This randomized phase II trial is studying rituximab to see how well it works compared with giving rituximab together with lenalidomide in treating patients with previously untreated follicular lymphoma.


Condition Intervention Phase
Lymphoma
Biological: Rituximab
Drug: lenalidomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rituximab Plus Lenalidomide or Rituximab Monotherapy for Untreated Patients With Follicular Lymphoma in Need of Therapy. A Randomized, Open-Label, Multicenter Phase II Trial.

Resource links provided by NLM:


Further study details as provided by Swiss Group for Clinical Cancer Research:

Primary Outcome Measures:
  • Complete response at week 23 [ Time Frame: at week 23 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Best overall response (OR) within 24 weeks [ Time Frame: within 24 weeks ] [ Designated as safety issue: No ]
  • Best Overall response (OR) within 12 weeks [ Time Frame: within 12 weeks ] [ Designated as safety issue: No ]
  • Best OR [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Duration of complete response [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Time to first off-trial anti-lymphoma therapy [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: n.a. ] [ Designated as safety issue: No ]
  • Adverse events, including laboratory abnormality assessments and vital signs [ Time Frame: n.a. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 152
Study Start Date: February 2011
Estimated Study Completion Date: December 2014
Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Rituximab
Rituximab (MabThera®) will be administered for a maximum of 8 infusions at weeks 1, 2, 3, 4 and again at weeks 12, 13, 14, 15 if the first restaging at week 10 (+/- 1 week) shows a partial response with at least more than 25% reduction in sum of product of diameters
Biological: Rituximab
Rituximab (MabThera®) will be administered for a maximum of 8 infusions at weeks 1, 2, 3, 4 and again at weeks 12, 13, 14, 15 if the first restaging at week 10 (+/- 1 week) shows a partial response with at least more than 25% reduction in sum of product of diameters
Other Name: Rituximab (MabThera)
Active Comparator: Rituximab plus Lenalidomide
Lenalidomide will be administered as 15 mg flat dose daily, starting 14 days before first and stopping 14 days after last rituximab administration.
Drug: lenalidomide
Lenalidomide will be administered as 15 mg flat dose daily, starting 14 days before first and stopping 14 days after last rituximab administration.
Other Name: Lenalidomide (Revlimid)

Detailed Description:

OBJECTIVES:

Primary

  • To determine the activity of rituximab in combination with lenalidomide versus rituximab alone in patients with previously untreated follicular lymphoma in need of therapy.

Secondary

  • To determine the safety of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to grade of disease (grades 1 or 2 vs 3a), presence of bulky disease (defined as masses ≥ 6 cm) (yes vs no), Follicular Lymphoma International Prognostic Index score (1 or 2 vs ≥ 3), and participating centers. Patients are randomized to 1 of 2 treatment arms.

  • Arm A: Patients receive rituximab IV on day 1 in weeks 1, 2, 3, 4 and weeks 12, 13, 14, 15 in the absence of disease progression or unacceptable toxicity.
  • Arm B: Patients receive rituximab IV as in arm A. Patients also receive oral lenalidomide once daily, starting 14 days before first rituximab administration and last until 14 days after the last rituximab administration, in the absence of disease progression or unacceptable toxicity.

All patients undergo restaging at week 10. Patients who show less than a minimal response (i.e., reduction of more than 25% in sum of product of diameters [SPD]) are off study treatment and transferred to the follow-up phase. Patients undergo a second restaging in week 23.

Some patients may undergo biopsies and blood and bone marrow sample collection periodically for biomarker studies.

After completion of study treatment, patients are followed up periodically for 20 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed follicular lymphoma

    • Stage III or IV disease OR stage II disease not suitable for radiotherapy
    • Grades 1, 2, or 3a disease
  • Previously untreated disease
  • CD20-positive disease
  • Patients in need of systemic therapy, meeting at least 1 of the following criteria:

    • Symptomatic enlarged lymph nodes, spleen, or other lymphoma manifestations
    • Bulky disease ≥ 6 cm in long diameter
    • Clinically significant progression over at least 6 months of any tumor lesion
    • Anemia (hemoglobin < 100 g/L) or thrombocytopenia (platelet count < 100 x 10^9/L) due to lymphoma
    • Clinically significant progressive decrease in hemoglobin or platelet count due to lymphoma
    • B-symptoms, weight loss > 10% within the past 6 months, drenching night sweats, or fever > 38°C not due to infection
  • At least one two-dimensionally measurable lesion with longest transverse diameter > 10 mm
  • Paraffin-embedded tumor tissue available
  • No known CNS involvement

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • EF ≥ 50% for patients with a history of cardiac disease or older than 70 years
  • Neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless due to Gilbert syndrome)
  • ALT ≤ 2.5 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN
  • Creatinine clearance ≥ 30 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception 4 weeks prior to, during, and for 12 months after completion of study therapy
  • Must be compliant and geographically proximal to allow for proper staging and follow-up
  • No serious underlying medical condition, at the judgment of the investigator, which could impair the ability of the patient to participate in the trial (e.g., active autoimmune disease or uncontrolled diabetes)
  • No malignancy within the past 3 years except for adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer
  • No psychiatric disorder precluding understanding information of trial-related topics, giving informed consent, or interfering with compliance for oral drug intake
  • No known hypersensitivity to trial drugs or hypersensitivity to any other components of the trial drugs
  • No known HIV positivity or hepatitis C infection
  • No serological evidence of current or past hepatitis B infection, unless the serological findings are clearly due to vaccination

PRIOR CONCURRENT THERAPY:

  • No prior systemic therapy for this disease
  • At least 3 months since prior radiotherapy
  • At least 30 days since prior treatment in another clinical trial
  • At least 4 weeks since prior and no concurrent corticosteroids unless administered as prophylaxis in at-risk patients for ≤ 3 days or at a dose equivalent to prednisone ≤ 15 mg/day, for indications other than lymphoma or lymphoma-related symptoms
  • No concomitant drugs contraindicated for use with the trial drugs
  • No other concurrent experimental drugs or anticancer therapy
  • No other concurrent investigational treatments
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01307605

Locations
Norway
Haukeland Hospital - University of Bergen
Bergen, Norway, N-5021
Sorlandet Sykehus HF Kristiansand
Kristiansand, Norway, 4604
Ullevaal University Hospital
Oslo, Norway, 0424
Helse Stavanger HF
Stavanger, Norway, 4068
University Hospital of North Norway - Tromso
Tromso, Norway, 9038
St. Olavs University Hospital
Trondheim, Norway, 7006
Sweden
Sahlgrenska University Hospital
Gothenburg, Sweden, S-413 45
University Hospital of Linkoping
Linkoping, Sweden, S-581 85
Sunderbyn Hospital
Lulea, Sweden, 95128
Lund University Hospital
Lund, Sweden, SE-22185
Karolinska University Hospital - Huddinge
Stockholm, Sweden, S-141 86
Karolinska University Hospital - Solna
Stockholm, Sweden, S-171 76
Sundsvall Hospital
Sundsvall, Sweden, 85186
Norrlands University Hospital
Umea, Sweden, S-90185
Uppsala University Hospital
Uppsala, Sweden, SE-75185
Switzerland
Kantonsspital Aarau
Aarau, Switzerland, 5001
Kantonsspital Baden
Baden, Switzerland, 5404
Universitaetsspital-Basel
Basel, Switzerland, 4031
Saint Claraspital AG
Basel, Switzerland, 4016
Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Bellinzona, Switzerland, 6500
Inselspital Bern
Bern, Switzerland, 3010
Spitalzentrum Oberwallis - Brig
Brig, Switzerland, 3900
Kantonsspital Bruderholz
Bruderholz, Switzerland, 4101
Kantonsspital Graubuenden
Chur, Switzerland, 7000
University Hospital
Geneva, Switzerland, 1211
Kantonsspital Liestal
Liestal, Switzerland, 4410
Kantonsspital Olten
Olten, Switzerland, 4600
Kantonsspital - St. Gallen
St. Gallen, Switzerland, 9007
Regionalspital
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, 8401
UniversitaetsSpital Zuerich
Zurich, Switzerland, 8091
Klinik Hirslanden
Zurich, Switzerland, 8032
City Hospital Triemli
Zurich, Switzerland, 8063
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
Study Chair: Emanuele Zucca, MD Istituto Oncologico della Svizzera Italiana - Ospedale San Giovanni
Study Chair: Eva K. Kimby, MD, PhD Karolinska Institutet
Principal Investigator: Felicitas Hitz, MD Cantonal Hospital of St. Gallen
Principal Investigator: Bjorn Ostenstad, MD Ullevaal University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: Swiss Group for Clinical Cancer Research
ClinicalTrials.gov Identifier: NCT01307605     History of Changes
Other Study ID Numbers: SAKK 35/10, SWS-SAKK-35-10, EUDRACT-2010-021253-39, EU-21107, CELGENE-SWS-SAKK-35/10
Study First Received: March 1, 2011
Last Updated: December 8, 2013
Health Authority: Switzerland: Swissmedic

Keywords provided by Swiss Group for Clinical Cancer Research:
contiguous stage II grade 1 follicular lymphoma
contiguous stage II grade 2 follicular lymphoma
contiguous stage II grade 3 follicular lymphoma
noncontiguous stage II grade 1 follicular lymphoma
noncontiguous stage II grade 2 follicular lymphoma
noncontiguous stage II grade 3 follicular lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Lenalidomide
Rituximab
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Antirheumatic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014